Peptide synthesis with 5-amino-1-methyl-1H-[1,2,4]triazole-3-carboxylic acid

In the search for the peptide synthesis of new potential lexitropsins, starting with methyl 5-amino-1-methyl-1H-[1,2,4]triazole-3-carboxylate 1a, we synthesized the chloroacetyl derivative of 2a, which was hydrolyzed to acid 2b and ammonolyzed to the peptide 2c. A more effective route was the use of (t-butoxycarbonyl)glycyl-benzotriazolide 3 to the acylation 1a, which leads the N/C protected peptide 4. This peptide was selectively N-deprotected to be the useful segment 5 for further peptide syntheses to the N-terminus. It was also C-deprotected, that is hydrolyzed to give peptide 2c for further C-extension. To the best of our knowledge, this is the first peptide that is a derivative of amino-1-methyl-1H-[1,2,4] triazole-carboxylic acid.